Clascoterone, sold under the brand name Winlevi, is an
antiandrogen
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking t ...
medication which is used
topically in the treatment of
acne
Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...
.
The medication is used as a
cream
Cream is a dairy product composed of the higher-fat layer skimmed from the top of milk before homogenization. In un-homogenized milk, the fat, which is less dense, eventually rises to the top. In the industrial production of cream, this proces ...
by
application to the skin, for instance the
face
The face is the front of the head that features the eyes, nose and mouth, and through which animals express many of their emotions. The face is crucial for human identity, and damage such as scarring or developmental deformities may affect th ...
and
scalp
The scalp is the area of the head where head hair grows. It is made up of skin, layers of connective and fibrous tissues, and the membrane of the skull. Anatomically, the scalp is part of the epicranium, a collection of structures covering th ...
.
Clascoterone is an antiandrogen, or
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.[androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...](_b ...<br></span></div> of the <div class=)
(AR), the
biological target
A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...
of
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
s such as
testosterone
Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
and
dihydrotestosterone
Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production o ...
.
It shows minimal
systemic absorption
Absorption may refer to:
Chemistry and biology
*Absorption (biology), digestion
**Absorption (small intestine)
*Absorption (chemistry), diffusion of particles of gas or liquid into liquid or solid materials
*Absorption (skin), a route by which su ...
when applied to
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different ...
.
Clascoterone was developed by Cassiopea and was approved for medical use in the United States in August 2020.
The US
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) considers it to be a
first-in-class medication
A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...
.
Medical uses
Clascoterone is
indicated
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
for the
topical
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
treatment of
acne vulgaris
Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...
in people aged twelve years of age and older.
Two large
phase III randomized controlled trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical ...
s evaluated the effectiveness of clascoterone for the treatment of acne over a period of 12 weeks.
Clascoterone decreased acne symptoms by about 8 to 18% more than
placebo
A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures.
Placebos are used in randomized clinical trials ...
.
The defined treatment success endpoint was achieved in about 18 to 20% of individuals with clascoterone relative to about 7 to 9% of individuals with placebo.
The comparative effectiveness of clascoterone between males and females was not described.
Side effects
The effects of local
skin reaction
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sys ...
s with clascoterone were similar to
placebo
A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures.
Placebos are used in randomized clinical trials ...
in two large phase III randomized controlled trials.
Suppression of the
hypothalamic–pituitary–adrenal axis
The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components: the hypothalamus (a part of the brain located below the thalamus), the pituitary gland ( ...
(HPA axis) may occur during clascoterone therapy in some individuals due to its
cortexolone metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
.
HPA axis suppression as measured by the
cosyntropin stimulation test was observed to occur in 3 of 42 (7%) of adolescents and adults using clascoterone for acne.
HPA axis function returned to normal within 4 weeks following discontinuation of clascoterone.
Hyperkalemia
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Oc ...
(elevated potassium levels) occurred in 5% of clascoterone-treated individuals and 4% of placebo-treated individuals.
Pharmacology
Pharmacodynamics
Clascoterone is a
steroidal antiandrogen
A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure. They are typically receptor antagonist, antagonists of the androgen receptor (AR) and act both by receptor antagonist, blocking the effects of androgens like ...
, or
antagonist
An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.[androgen receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...](_b ...<br></span></div> of the <div class=)
(AR), the
biological target
A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...
of
androgen
An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
s such as
testosterone
Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
and
dihydrotestosterone
Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production o ...
(DHT).
In a
bioassay
A bioassay is an analytical method to determine the potency or effect of a substance by its effect on animal testing, living animals or plants (''in vivo''), or on living cells or tissues (''in vitro''). A bioassay can be either quantal or quantit ...
, the topical potency of the medication was greater than that of
progesterone
Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...
,
flutamide
Flutamide, sold under the brand name Eulexin among others, is a nonsteroidal antiandrogen (NSAA) which is used primarily to treat prostate cancer. It is also used in the treatment of androgen-dependent conditions like acne, hirsutism, excessive ...
, and
finasteride
Finasteride, sold under the brand names Proscar and Propecia among others, is a medication used to treat pattern hair loss and benign prostatic hyperplasia (BPH) in men. It can also be used to treat hirsutism, excessive hair growth in women. It ...
and was equivalent to that of
cyproterone acetate
Cyproterone acetate (CPA), sold alone under the brand name Androcur or Ethinylestradiol/cyproterone acetate, with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the tre ...
.
Likewise, it is significantly more
efficacious
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made between ...
as an antiandrogen than other AR antagonists such as
enzalutamide and
spironolactone
Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...
in
scalp
The scalp is the area of the head where head hair grows. It is made up of skin, layers of connective and fibrous tissues, and the membrane of the skull. Anatomically, the scalp is part of the epicranium, a collection of structures covering th ...
dermal papilla cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
* Cellphone, a phone connected to a cellular network
* Clandestine cell, a penetration-resistant form of a secret or outlawed organization
* Electrochemical cell, a de ...
s and
sebocytes ''
in vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
''.
Pharmacokinetics
Steady-state
In systems theory, a system or a process is in a steady state if the variables (called state variables) which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those properties ''p'' ...
levels of clascoterone occur within 5 days of twice daily administration.
At a dosage of 6 g clascoterone cream applied twice daily,
maximal circulating levels of clascoterone were 4.5 ± 2.9 ng/mL,
area-under-the-curve levels over the dosing interval were 37.1 ± 22.3 h*ng/mL, and
average
In colloquial, ordinary language, an average is a single number or value that best represents a set of data. The type of average taken as most typically representative of a list of numbers is the arithmetic mean the sum of the numbers divided by ...
circulating levels of clascoterone were 3.1 ± 1.9 ng/mL.
In rodents, clascoterone has been found to possess strong local antiandrogenic activity, but negligible systemic antiandrogenic activity when administered via
subcutaneous injection
Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion.
A subcutaneous injection is administered as a bolus (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...
.
Along these lines, the medication is not
progonadotropic in animals.
The
plasma protein binding
Plasma protein binding refers to the degree to which medications attach to blood proteins within the blood plasma. A drug's efficacy may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse o ...
of clascoterone is 84 to 89% regardless of concentration.
Clascoterone is rapidly
hydrolyzed
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysi ...
into
cortexolone (11-deoxycortisol) and this compound is a possible primary
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
of clascoterone based on ''
in-vitro'' studies in human
liver cell
The liver is a major metabolic organ exclusively found in vertebrates, which performs many essential biological functions such as detoxification of the organism, and the synthesis of various proteins and various other biochemicals necessary ...
s.
During treatment with clascoterone, cortexolone levels were detectable and generally below or near the low limit of quantification (0.5 ng/mL).
Clascoterone may also produce other metabolites, including
conjugates.
The
elimination of clascoterone has not been fully characterized in humans.
Chemistry
Clascoterone, also known as cortexolone 17α-propionate or 11-deoxycortisol 17α-propionate, as well as 17α,21-dihydroxyprogesterone 17α-propionate or 17α,21-dihydroxypregn-4-en-3,20-dione 17α-propionate, is a
synthetic
Synthetic may refer to:
Science
* Synthetic biology
* Synthetic chemical or compound, produced by the process of chemical synthesis
* Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...
pregnane
Pregnane, also known as 17β-ethylandrostane or as 10β,13β-dimethyl-17β-ethylgonane, is a C21 steroid and, indirectly, a parent of progesterone. It is a parent hydrocarbon for two series of steroids stemming from 5α-pregnane (originally all ...
steroid
A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration.
Steroids have two principal biological functions: as important components of cell membranes t ...
and a
derivative
In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...
of
progesterone
Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...
and
11-deoxycortisol (cortexolone).
It is specifically the C17α
propionate ester
In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...
of 11-deoxycortisol.
An
analogue of clascoterone is
9,11-dehydrocortexolone 17α-butyrate (CB-03-04).
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...
s related to clascoterone, for instance
cortisone acetate and
prednisolone acetate, show antiandrogenic activity in animals similarly to clascoterone.
History
C17α esters of 11-deoxycortisol were unexpectedly found to possess antiandrogenic activity.
Clascoterone, also known as cortexolone 17α-propionate, was selected for development based on its optimal drug profile.
The medication was approved by the US
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) for the treatment of acne in August 2020.
The FDA approved clascoterone based on evidence from two clinical trials (Trial 1/NCT02608450 and Trial 2/NCT02608476) of 1,440 participants 9 to 58 years of age with acne vulgaris.
The trials were conducted at 99 sites in the United States, Poland, Romania, Bulgaria, Ukraine, Georgia, and Serbia.
[ ] Participants applied clascoterone or vehicle (placebo) cream twice daily for 12 weeks.
Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.
The benefit of clascoterone in comparison to placebo was assessed after 12 weeks of treatment using the Investigator's Global Assessment (IGA) score that measures the severity of disease (on a scale from 0 to 4) and a decrease in the number of acne lesions.
Society and culture
Legal status
In April 2025, the
European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
(EMA) recommended the refusal of a marketing authorization for Winlevi, a medicine intended for treating acne vulgaris.
[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.] The EMA noted that Winlevi is a new class of medicine that blocks receptors for androgens.
However, there is a risk of the medicine suppressing the working of three organs: the hypothalamus and pituitary glands in the brain and adrenal glands.
The suppression of these organs could lead to impaired growth and sexual maturation, which is a major concern in adolescents.
Although the company presented data to show that the risk was low, the EMA considered that these data, as well as measures the company proposed to minimize the risk, were not sufficient to approve the medicine for people from 12 years of age to less than 18 years of age.
In May 2025, Cassiopea requested a re-examination of the EMA's April 2025 opinion.
Names
Clascoterone is the
international nonproprietary name and the
United States Adopted Name
A United States Adopted Name (USAN) is a unique nonproprietary name assigned to a medication marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association (AMA), the United St ...
.
Research
Clascoterone has been suggested as a possible treatment for
hidradenitis suppurativa
Hidradenitis suppurativa (HS), sometimes known as acne inversa or Verneuil's disease, is a long-term dermatological condition characterized by the occurrence of inflamed and swollen lesions, lumps. These are typically painful and break open, r ...
(acne inversa), an androgen-dependent skin condition.
It is also under development in a higher concentration for the treatment of
androgen-dependent scalp hair loss
Pattern hair loss (also known as androgenetic alopecia (AGA)) is a hair loss condition that primarily affects the top and front of the scalp. In male-pattern hair loss (MPHL), the hair loss typically presents itself as either a receding front h ...
.
References
External links
*
*
{{Authority control
Antiandrogen esters
Diketones
Pregnanes
Propionate esters
Steroidal antiandrogens
Anti-acne preparations